Novel cancer gene accelerates or stops tumour growth

May 27, 2009
By Matet Nebres

(PhysOrg.com) -- Researchers at the Hospital for Sick Children (SickKids) and the University of Toronto have found a gene that plays a crucial role in the development of rhabdomyosarcoma - the most common childhood sarcoma (soft tissue cancer). The gene is called integrin-linked kinase (ILK) and is unique in that it can act as both a tumour suppressor and a tumour promoter. The study is published in the June issue of The Journal of Clinical Investigation.

"Think of tumour growth as a car; most genes either act to drive the growth, or to put the brakes on it. We were surprised to find that in patients who had different types of rhabdomyosarcoma, ILK could act as either the brake pedal or the accelerator," said Dr. David Malkin, a professor in the Department of Paediatrics at the University of Toronto, pediatric oncologist and senior scientist at SickKids.

Rhabdomyosarcoma (RMS) originates in muscle tissue and comes in two forms: embryonal RMS and alveolar RMS. Scientists have found that in patients with embryonal RMS, the ILK gene acted like the brakes and high levels of ILK suppressed tumour growth. However, in patients with alveolar RMS, ILK acted like the gas pedal, promoting the growth of tumours.

"Having found that ILK could act both as a tumour suppressor and a promoter, we needed to find out what was causing the gene to change its behaviour," said Adam Durbin, lead author of the study and a University of Toronto MD/PhD student. "We determined that it must be something that ILK was communicating with."

The researchers found the culprit was another protein in the cell called JNK1 (pronounced "Junk-1"), which can act to control cell growth and cell death. The scientists determined that the levels of this protein dictated whether the ILK gene acted like the gas pedal or the brakes.

By understanding the mechanism behind this interaction, the scientists hope to be able to improve treatment options for RMS patients. There are about 135 new cases of RMS in Canada every year. The cancer is commonly found in two age groups; in children aged two to three and then at a later stage, in teenagers. Depending on the type and stage of RMS, the survival rate can be as low as 20 to 30 per cent. Like many cancer therapies, the current treatment for RMS is toxic and debilitating, so doctors are looking for ways to more effectively target the cancer cells while enabling healthy cells to remain intact.

In their study, the scientists found the gas pedal could be destroyed by knocking out the gene using genetic manipulation in mice.

The researchers say new drug treatments for RMS may not be too far off in the future. There are drugs in early clinical trials that are currently being tested for their ability to turn off or inhibit ILK in other cancers. However to turn on ILK, new drugs would need to be developed.

"A significant element of this study is that ILK is not unique to RMS; this gene is found in many other types of cancers," said Malkin. "The key would be to try to find the right way to kill the gas pedal and not the brakes."

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